Association of elevated blood pressure during exercise with cerebral white matter lesions.

OBJECTIVES: Cerebral white matter lesions (WMLs) are regarded to be subclinical ischemic changes of the cerebral parenchyma. Many previous studies have shown that baseline blood pressure (BP) is one of the most important factors for WMLs, but the relation between exercise BP and WMLs has not been fully evaluated. So, we sought to investigate the relationships between cerebral WMLs and peak exercise BP. METHODS: Brain magnetic resonance imaging scan and treadmill testing were performed simultaneously in 130 consecutive subjects without history of stroke or transient ischemic stroke. RESULTS: Among 130 subjects, 42 individuals (32%) presented WMLs. Individuals with WMLs were older than those without WMLs, and baseline systolic BP and pulse pressure were higher in subjects with WMLs. During treadmill test, peak exercise systolic BP was more significantly elevated in subjects with WMLs. In multivariable logistic regression analysis, elevated baseline systolic BP, not peak exercise systolic BP, was associated with the presence of WMLs, independently of age. However, in multivariable logistic regression analysis of 88 normotensive subjects, elevated peak systolic BP during exercise was the only determinant for the presence of WMLs. CONCLUSIONS: Elevated peak systolic BP during exercise is significantly related with WMLs, subclinical small vessel disease of brain, especially in normotensive subjects.

Association of insulin resistance and coronary artery remodeling: an intravascular ultrasound study.

BACKGROUND: There are few studies that investigated the correlation between insulin resistance (IR) and the coronary artery remodeling. The aim of the study is to investigate the association of IR measured by homeostasis model assessment of insulin resistance (HOMA-IR) and coronary artery remodeling evaluated by intravascular ultrasound (IVUS). METHODS: A total of 298 consecutive patients who received percutaneous coronary interventions under IVUS guidance were retrospectively enrolled. The value of HOMA-IR more than 2.5 was considered as IR positive. Metabolic syndrome was classified according to NCEP ATP III guidelines. The remodeling index was defined as the ratio of the external elastic membrane (EEM) area at the lesion site to the EEM area at the proximal reference site. RESULTS: A total of 369 lesions were analyzed (161 lesions in HOMA-IR positive and 208 lesions in HOMA-IR negative). Remodeling index was significantly higher in the HOMA-IR positive group compared with the negative group (HOMA-IR positive vs. negative: 1.074 ± 0.109 vs. 1.042 ± 0.131, p = 0.013). There was a significant positive correlation between remodeling index and HOMA-IR (p = 0.010). Analysis of HOMA-IR according to remodeling groups showed increasing tendency of HOMA-IR, and it was statistically significant (p = 0.045). Multivariate analysis revealed that only HOMA-IR was an independent predictor of remodeling index (r = 0.166, p = 0.018). CONCLUSION: Increased IR estimated by HOMA-IR was significantly associated with a higher remodeling index and positive coronary artery remodeling.

The additive value of multiple biomarkers in prediction of premature coronary artery disease.

OBJECTIVE: The aim of this study was to determine the value of additional multiple biomarkers in the prediction of premature coronary artery disease (CAD). METHODS AND RESULTS: Data from 503 CAD patients and 503 healthy control patients with matching age and sex were collected. The patient group consisted of male (25 to 55 years) and female (30 to 60 years) patients with documented angiographic multi-vessel CAD. Baseline characteristics of conventional risk factors and biomarkers were collected. We compared the conventional risk factors model with the model with six additional biomarkers (hs-CRP, IL-6, RAGE, Lp-LPA2, adiponectin, and RANTES), which have shown significant association with premature CAD. We also evaluated the effects of adding each of the six biomarkers to the conventional laboratory data. The additional biomarkers model resulted in improvements in the C-statistic (0.953 vs. 0.937, P=0.0003) in comparison with the conventional risk factors model. Among the 6 biomarkers added to the patient group, hs-CRP and IL-6 had a significant discriminative power to predict the risk of premature CAD (hs-CRP; P = 0.0005, IL-6; P= 0.003). CONCLUSIONS: Although conventional risk factors were more strongly associated with premature CAD than were biomarkers, adding the 6 biomarkers (hs-CRP, IL-6, RAGE, Lp-LPA2, adiponectin, and RANTES) improved the prediction of premature CAD moderately. We found that hs-CRP and IL-6 had shown a significant contribution in the prediction of premature CAD.

Extent of late gadolinium enhancement on cardiovascular magnetic resonance imaging and its relation to left ventricular longitudinal functional reserve during exercise in patients with hypertrophic cardiomyopathy.

BACKGROUND: The aim of this study was to investigate whether the extent of late gadolinium enhancement (LGE) on cardiovascular magnetic resonance imaging reflecting myocardial fibrosis correlates with left ventricular (LV) longitudinal function during exercise in hypertrophic cardiomyopathy (HCM). METHODS AND RESULTS: Mitral annular velocities (E' and S') were measured on echocardiography at rest and during graded bicycle exercise (25 W, 3-min increments) in 46 HCM patients (mean age, 53 years; 32 men). LV longitudinal diastolic and systolic functional reserve indices were calculated as ΔE'×E'base and ΔS'×S'base, where ΔE' and ΔS' are the changes in E' and S' from baseline to 50 W of exercise, respectively. The patients were divided into 2 groups according to the extent of LGE (as "percentage of LV mass containing LGE": %LV with LGE; range, 0-37%; median, 6%): group 1 (n=23), %LV with LGE <6%, and group 2, %LV with LGE ≥6%. Baseline echocardiographic parameters were similar between the 2 groups, but changes in E' and S' during exercise were smaller in group 2 (ΔE': 2.8±1.8 cm/s vs.1.5±1.0 cm/s, P=0.007; ΔS': 2.2±1.2 cm/s vs. 0.9±0.8 cm/s, P<0.0001). LV functional reserve indices were also significantly lower in group 2 (ΔE'×E'(base): 12.8±7.7 vs. 5.5±3.4, P=0.001; ΔS'×S'(base): 12.6±7.4 vs. 4.7±4.5, P<0.0001). CONCLUSIONS: LV longitudinal function during exercise is influenced by the extent of LGE in HCM. Myocardial fibrosis may represent a pathologic substrate that determines LV functional reserve in patients with HCM.

Incidence and natural history of coronary artery aneurysm developing after drug-eluting stent implantation.

AIMS: There is a growing concern about the occurrence of coronary artery aneurysms (CAAs) after drug-eluting stent (DES) implantation and their long-term course. We assessed the occurrence and the factors affecting the long-term outcome of DES-associated CAA. METHODS AND RESULTS: We analyzed 3,612 consecutive patients (4,419 lesions) who underwent follow-up angiography after DES implantation. All 34 CAAs (0.76% per lesion) in 29 patients (0.8% per patient) were detected at follow-up, and the mean elapsed time from DES implantation to CAA diagnosis was 414 ± 213 days. Angiographically, CAAs developed almost exclusively in complex (type B2/C) de novo lesions (30 [88.2%] of 34 lesions), and lesion length was significantly greater in patients with CAA than without CAA (26.9 ± 9.03 vs 23.1 ± 7.14 mm; P = .004). Myocardial infarction with stent thrombosis occurred in 5 patients with CAA (17.2%), 4 of whom were on aspirin only without clopidogrel. CONCLUSION: Although CAAs rarely develop after DES implantation and show mostly favorable clinical courses, long-term maintenance of clopidogrel therapy might be required to minimize occurrence of adverse clinical events resulting from stent thrombosis.

Soluble fms-like tyrosine kinase-1 and the progression of carotid intima-media thickness ­ 24-month follow-up study ­.

BACKGROUND: The relationship between fms-like tyrosine kinase-1 (sFlt-1), a soluble receptor for vascular endothelial growth factor (VEGF), and vascular disease has not been established, so this study aimed to elucidate the association between sFlt-1 and the progression of carotid intima - media thickness (IMT) in hypertensive patients. METHODS AND RESULTS: The 120 hypertensive patients under medical control were enrolled and 112 completed the study (age 59 ± 9 years, 57 females). Plasma VEGF and sFlt-1 levels were measured at enrollment. At baseline and 24-month visit, carotid IMT was measured and the association between sFlt-1 and IMT progression was assessed by linear regression. At baseline, age (r=0.186) and low level of high-density lipoprotein-cholesterol (HDL-C <40 mg/dl, r=0.214) were significantly related to carotid IMT. Over the 24 months, carotid IMT increased from 0.670 ± 0.089 mm to 0.696 ± 0.095 mm. There was a positive correlation between sFlt-1 tertiles and IMT change (P=0.05 by ANOVA). Upon multivariate analysis, log-transformed sFlt-1 level (ß=0.137, P=0.003) and low HDL-C (ß=0.048, P=0.04) were identified as predictors of IMT progression, independent of other confounding variables. CONCLUSIONS: High sFlt-1 level is predictive of carotid IMT progression in hypertensive patients. Low HDL-C level was also associated with IMT change. These observations support a high sFlt-1 level being indicative of progression of atherosclerosis.

Delayed enhancement magnetic resonance imaging is a significant prognostic factor in patients with non-ischemic cardiomyopathy.

BACKGROUND: Delayed enhancement (DE) on cardiac magnetic resonance imaging (CMR) is a marker of myocardial fibrosis. The absence of DE in CMR is a predictor of left ventricular (LV) functional improvement in patients with non-ischemic cardiomyopathy (NICM), so in the present study it was investigated whether presence of DE has prognostic significance in patients with NICM at long-term follow-up. METHODS AND RESULTS: The 79 patients (56.4+/-13.5 years, 48 males) with NICM (LV ejection fraction <35%, no significant coronary artery disease) were monitored for occurrence of cardiac events. CMR was performed to assess DE. Cardiac events were defined as rehospitalization (because of worsening of heart failure), cardiac transplantation or death. There were 37 patients without and 42 patients with DE. The mean follow-up duration was 19+/-10 months. There was 1 event (2.7%, 1 rehospitalization) in the DE (-) group, whereas 13 events (30.9%, 1 death, 1 transplantation, 11 rehospitalizations) occurred in the DE (+) group. The event-free survival was significantly longer in the DE (-) group than in the DE (+) group (38.9+/-1.0 vs 28.4+/-2.7 months, P<0.01). Multivariate regression analysis revealed that presence of DE was the most potent, independent predictor of cardiac events (hazard ratio 8.06, confidence interval 1.03+/-63.41, P<0.05). CONCLUSIONS: The presence of DE in CMR is a significant predictor of future cardiac events in patients with NICM.

Blood eicosapentaenoic acid and docosahexaenoic acid as predictors of all-cause mortality in patients with acute myocardial infarction--data from Infarction Prognosis Study (IPS) Registry.

BACKGROUND: Although omega-3 polyunsaturated fatty acids are known to have beneficial effects on cardiovascular diseases, their prognostic value has not been studied prospectively in patients with acute myocardial infarction (AMI). METHODS AND RESULTS: The plasma levels of phospholipids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) (% of total fatty acids), were measured in 508 patients (365 males; mean age, 63 years) with AMI. Clinical and biomarker predictors of all-cause and cardiovascular mortality were identified by stepwise Cox regression model. During a mean follow-up of 16.1 months, 36 (7.1%) patients died. After controlling for confounding variables, age (hazard ratio (HR): 1.09, P<0.001), renal insufficiency (HR: 2.84, P=0.01) and EPA level (HR: 0.29, P=0.004) were identified as independent predictors of all cause-mortality. When stratified by gender, age (HR: 1.08, P=0.001) and renal insufficiency (HR: 4.49, P=0.003) were predictors of all-cause-mortality in males, whereas EPA level (HR: 0.18, P=0.009) and angiotensin-converting enzyme inhibitor use (HR: 0.24, P=0.03) were identified as predictive of all-cause-mortality in females. CONCLUSIONS: Lower plasma level of EPA, but not DHA, was an independent predictor for all-cause-mortality in patients with AMI, but this relationship was significant only in female patients.

Effects of hemoglobin concentration and creatinine clearance in pro-B-type natriuretic peptide-based left ventricular filling pressure prediction in patients with preserved left ventricular systolic function.

Although N-terminal pro-B-type natriuretic peptide (pro-BNP) has been shown to correlate with left ventricular (LV) filling pressure, pro-BNP-based LV filling pressure prediction has some limitations due to several factors that affect pro-BNP. The aim of this study was to evaluate the effects of blood hemoglobin concentration and creatinine clearance (CCr) on pro-BNP-based LV filling pressure prediction in patients with preserved LV systolic function. A total of 421 consecutive patients referred for coronary angiography underwent LV pressure measurement by fluid-filled catheters. Patients with plasma creatinine levels>or=1.5 mg/dl and LV ejection fractions<50% were excluded. LV diastolic pressures and echocardiographic parameters were compared with pro-BNP levels in 281 patients. Blood hemoglobin levels and CCr were measured simultaneously. Log pro-BNP was independently correlated with hemoglobin concentration (beta=-0.261, p<0.001), CCr (beta=-0.230, p<0.001) and LV pre-A-wave pressure (beta=0.384, p<0.001). A pro-BNP level of 124 pg/ml was the optimal cutoff for LV pre-A-wave pressure>15 mm Hg in all patients (sensitivity 67%, specificity 67%, p<0.001). However, by subclassification according to hemoglobin and CCr tertiles, optimal cut-off values varied significantly, and their predictive accuracies could be improved (from 89 to 331 pg/dl, with diagnostic accuracy up to 79%). In conclusion, in the pro-BNP-based prediction of elevated LV filling pressure, subclassification on the basis of hemoglobin concentration and CCr should be considered in patients with preserved LV systolic and renal function.

The inhibition of insulin-stimulated proliferation of vascular smooth muscle cells by rosiglitazone is mediated by the Akt-mTOR-P70S6K pathway.

PURPOSE: Thiazolidinediones (TZDs) are known to inhibit the proliferation of vascular smooth muscle cell (VSMC) by increasing the activity of p27Kip1 and retinoblastoma protein (RB). However, the upstream signaling mechanisms associated with this pathway have not been elucidated. The Akt-mTOR-P70S6 kinase pathway is the central regulator of cell growth and proliferation, and increases cell proliferation by inhibiting the activities of p27Kip1 and retinoblastoma protein (RB). Therefore, we hypothesized in this study that rosiglitazone inhibits VSMC proliferation through the inhibition of the Akt-TOR-P70S6K signaling pathway. MATERIALS AND METHODS: Rat aortic smooth muscle cells (RAoSMCs) were treated with 10microM of rosiglitazone 24 hours before the addition of insulin as a mitogenic stimulus. Western blot analysis was performed to determine the inhibitory effect of rosiglitazone treatment on the Akt-mTOR-P70S6K signaling pathway. Carotid balloon injury was also performed in Otsuka Long-Evans Tokushima Fatty (OLETF) diabetic rats that were pretreated with 3 mg/kg of rosiglitazone. RESULTS: Western blot analysis demonstrated significant inhibition of activation of p-Akt, p-m-TOR, and p-p70S6K in cells treated with rosiglitazone. The inhibition of the activation of the p-mTOR-p-p70S6K pathway seemed to be mediated by both the upstream PI3K pathway and MEK-ERK complex. CONCLUSION: The inhibitory effect of rosiglitazone on RAoSMC proliferation in vitro and in vivo is mediated by the inhibition of the Akt-mTOR-P70S6K pathway.

Incremental value of measuring the time difference between onset of mitral inflow and onset of early diastolic mitral annulus velocity for the evaluation of left ventricular diastolic pressures in patients with normal systolic function and an indeterminate E/E'.

This study sought to evaluate the incremental value of the time interval between the onset of early transmitral flow velocity (E) and the onset of early diastolic velocity (E') of the mitral annulus for the prediction of left ventricular (LV) end-diastolic pressure (EDP) in the presence of a "gray zone" value for E/E'. An E/E' ratio of 8 to 15 is classified as the "gray zone" for the estimation of LVEDP. Recently, it was suggested that prolongation of the time interval between the onset of E and E' (T(E'-E)) might indicate elevated filling pressure. Simultaneous left-sided cardiac catheterization and Doppler echocardiography were performed in 74 patients with normal systolic function. T(E'-E) was calculated as the time interval between the peak of the R wave and the onset of E' and between the peak of the R wave and the onset of E. Of the 74 patients enrolled, 55 (27 men, mean age 59 years) who had E/E' ratios of 8 to 15 were analyzed. LVEDP was elevated (>18 mm Hg) in 34 patients (62%). There was no significant difference in Doppler echocardiographic parameters and N-terminal pro-brain natriuretic peptide levels between those with normal and high LVEDP, except T(E'-E), which was significantly longer in the latter (19.0 +/- 17.8 vs 35.0 +/- 17.0 ms, p = 0.002). The receiver-operating characteristic curves for the prediction of high LVEDP showed the largest area under the curve (0.760) for T(E'-E). In multivariate analysis, T(E'-E) added significant information to the other parameters in the prediction of high LVEDP (p = 0.029). In conclusion, T(E'-E) may have an incremental value in the estimation of LVEDP in patients with normal systolic function and indeterminate E/E' ratios.

Comparison of long-term outcome after mitral valve replacement or repeated balloon mitral valvotomy in patients with restenosis after previous balloon valvotomy.

Symptomatic mitral stenosis (MS) develops in 7% to 21% of patients after percutaneous mitral balloon valvotomy (PMV). Treatment options for these patients are surgical mitral valve replacement (MVR) or repeated PMV. However, no comparisons were made between these 2 procedures regarding long-term outcome. This retrospective study compares the long-term outcome of 888 patients with symptomatic MS after MVR or repeated PMV who underwent PMV from April 1988 to December 2003. Thirty-two patients subsequently underwent repeated PMV, and 59 patients underwent MVR for symptomatic MS. Mean follow-up was 85 +/- 43 months with a maximum follow-up of 15 years. Patients with MVR have more unfavorable clinical characteristics, including a higher incidence of atrial fibrillation and severe mitral regurgitation. Event-free survival was similar between the 2 groups up to 40 months after the procedure; 3-year event-free survival rates were 96.6% for MVR patients and 90.0% for repeated PMV patients (p = 0.215). However, after 40 months, the outcome was more favorable for MVR. Comparing MVR versus PMV, 6-year event-free survival rates were 93.0% versus 75.9% (p = 0.036), and 9-year event-free survival rates were 90.4% versus 36.0% (p <0.001). In conclusion, the long-term outcome of patients with symptomatic MS after previous PMV was more favorable after MVR than after repeated PMV. These data suggest that MVR may be the preferred mode of therapy in patients with unfavorable valve morphologic characteristics and no co-morbid disease.

Delayed hyperenhancement magnetic resonance imaging is useful in predicting functional recovery of nonischemic left ventricular systolic dysfunction.

BACKGROUND: About 25% of the patients with nonischemic left ventricular (LV) systolic dysfunction improve spontaneously. However, the predictors for functional improvement are not known. We hypothesized that myocardial fibrosis, assessed by cardiac magnetic resonance (CMR) imaging, may predict the reversibility of nonischemic LV systolic dysfunction. METHODS AND RESULTS: CMR was performed in 46 patients. Baseline and follow-up echocardiography was performed to assess the recovery of LV function. There were 24 patients with absence of delayed hyperenhancement (group 1) and 22 patients with delayed hyperenhancement (group 2). There were significant difference for the follow-up LV end-diastolic dimension (56.2 +/- 7.3 versus 62.6 +/- 11.9), LV end-systolic dimension (43.2 +/- 9.2 versus 52.8 +/- 12.6), and LV ejection fraction (LVEF) (46.8 +/- 12.4% versus 31.6 +/- 11.3%). Follow-up echocardiography of 19/24 (79.2%) patients in group 1 showed functional recovery, whereas only 2/22 (9.1%) patient in group 2 showed functional recovery. The absence of delayed hyperenhancement was associated with sensitivity, specificity, positive predictive value, and negative predictive value of 90.5%, 79.2%, 80.0%, and 90.9%, respectively. CONCLUSION: Absence of delayed hyperenhancement demonstrated excellent sensitivity and negative predictive value in predicting functional recovery of nonischemic LV systolic dysfunction.

Inflammatory and vasoactive factors in the aspirate from the culprit coronary artery of patients with acute myocardial infarction.

BACKGROUND: Besides distal embolization of thrombus and plaque debris, locally increased inflammatory markers at the site of ruptured plaque in acute myocardial infarction (AMI) are thought to have an adverse impact on myocardial reperfusion during primary percutaneous coronary intervention (PCI). However, there is lack of data on such factors. Therefore, we investigated the presence of locally increased inflammatory and vasoactive factors in culprit coronary artery. METHODS: We performed primary PCI with PercuSurge GuideWire system in 18 AMI patients. We collected blood samples from the femoral artery before PCI and from culprit coronary artery after first predilation while inflating the distal protection balloon and after completing PCI. We determined concentrations of C-reactive protein, soluble CD40 ligand, Interleukin (IL-6), serotonin, tissue factor, and factor VIIa. RESULTS: While the concentrations of soluble CD40 ligand (2.84+/-3.74 vs 0.98+/-0.63 ng/mL, p=0.004), IL-6 (33.67+/-32.63 vs 17.08+/-21.41 pg/mL, p<0.001), serotonin (2.05+/-0.76 vs 0.92+/-0.60 ng/mL, p<0.001), tissue factor (257.17+/-84.34 vs 154.60+/-87.99 pg/mL, p<0.001) and factor VIIa (34.30+/-27.30 vs 24.19+/-28.00 ng/mL, p=0.016) were significantly higher in the culprit coronary artery than in the femoral artery, CRP levels did not differ. The locally elevated concentrations of various factors were successfully reduced after multiple aspirations of blood using the PercuSurge GuideWire system. CONCLUSIONS: We found increased levels of soluble CD40 ligand, IL-6, serotonin, tissue factor and factor VII in the culprit coronary artery compared to those in peripheral blood. The clinical impact of such locally increased soluble factors in the culprit coronary artery needs to be investigated in further studies.

miRNA polymorphisms (miR­146a, miR­149, miR­196a2 and miR­499) are associated with the risk of coronary artery disease.

Small non­coding microRNAs (miRNAs) are not only important for heart and vascular development but are also important in cardiovascular pathophysiology and diseases, such as ischemia and atherosclerosis­related diseases. However, the effect of miR­146a, miR­149, miR­196a2 and miR­499 polymorphisms on coronary artery disease (CAD) susceptibility remain unknown. The aim of the present study was to examine the genotype frequencies of miR­146a, miR­149, miR­196a2 and miR­499 polymorphisms in patients with CAD, and assess their clinical applications for diagnosing and monitoring CAD. Using polymerase chain reaction­amplified DNA, microRNA polymorphisms were analyzed in 522 patients with CAD and 535 control subjects. The miR­149 rs2292832 C>T and miR­196a2 rs11614913 T>C polymorphisms were shown to be significantly associated with CAD prevalence. In subgroup analyses according to disease severity, the miR­146a rs2910164GG genotype was significantly associated with CAD risk in the stent ≥2 group. In addition, miR­146aG/­149T/­196a2C/­499 G allele combination was significantly associated with CAD prevalence (G­T­C­G and G­C­C­G of miR­146a/­149/­196a2/­499). The combination genotypes of miR­146aGG/149TC+CC and miR­149CC/196a2TC were significantly associated with CAD incidence. In subgroup analyses, miR­146a rs2910164 C>G increased the risk of developing CAD in non­smoking, hypertensive and nondiabetic subgroups. Furthermore, miR­149 rs2292832 C>T and miR­196a2 rs11614913 T>C was shown to increase CAD risk in females and patients aged >63 years old. The miR­149T allele, miR­196a2C allele and miR­146aG/­149T/­196a2C/­499 G allele combination were associated with CAD pathogenesis. The combined effects of environmental factor and genotype combination of miRNA polymorphisms may contribute to CAD prevalence.

Can pro-brain natriuretic peptide be used as a noninvasive predictor of elevated left ventricular diastolic pressures in patients with normal systolic function?

OBJECTIVES: This study was sought to investigate whether plasma N-terminal pro-brain natriuretic peptide (proBNP) can help identify patients with an elevated left ventricular end-diastolic pressure (LVEDP) or filling pressures in patients with a normal systolic function. BACKGROUND: The proBNP is a good predictor of an elevated LVEDP in patients with a systolic dysfunction. However, whether proBNP can predict an elevated LVEDP in patients with a normal systolic function remains to be determined. METHODS: The LV pressures were measured by fluid-filled catheters in 216 patients (125 men, mean age 60 +/- 10 years) with a normal systolic function (ejection fraction 66% +/- 8%, range 50%-81%) who were undergoing diagnostic cardiac catheterization. The proBNP was sampled at the time of cardiac catheterization and was measured using a quantitative electrochemiluminescence immunoassay. RESULTS: The log-transformed proBNP levels correlated significantly with the LVEDP (r = 0.33, P = .001) and LV pre-A-wave pressure (pre-A pressure) (r = 0.31, P = .001). An elevated proBNP, defined as >315 pg/mL, predicted an LVEDP > or = 15 mm Hg with a sensitivity of 16% and a specificity of 95% as well as a pre-A pressure > or = 15 mm Hg with a sensitivity of 36% and a specificity of 95%. However, among the 93 patients with an LVEDP > or = 15 mm Hg, 77 (83%) patients had a normal proBNP concentration (< 315 pg/mL). CONCLUSION: The proBNP level showed weak correlations with the LVEDP and LV pre-A pressure in patients with a normal systolic function. Although high proBNP levels can predict an elevated LV diastolic pressure with high specificity, the sensitivity was quite low. Because the majority of patients with an elevated LVEDP had a normal proBNP, the proBNP level may not be suitable as a screening test for assessing LV filling pressures in the presence of normal systolic function.

Comparison of effects of drug-eluting stents versus bare metal stents on plasma C-reactive protein levels.

After coronary stenting, inflammatory mechanisms play a crucial role in the pathogenesis of neointimal proliferation and in-stent restenosis. Drug-eluting stents (DESs) have been shown to decrease in-stent restenosis in different studies. We compared plasma C-reactive protein (CRP) levels after DES implantation with levels after bare metal stent (BMS) implantation. We performed percutaneous coronary intervention with a single stent in 67 patients (54 men; 59 +/- 9 years of age; n = 21 in the BMS group, n = 46 in the DES group) who had stable angina. Plasma CRP levels were determined before intervention and at 48 hours, 72 hours, and 2 weeks after coronary stenting. There was no difference in clinical and angiographic baseline characteristics except that the DES group had more patients with diabetes (34.8% vs 9.5%, p = 0.04), smaller reference vessels (2.95 +/- 0.53 vs 3.29 +/- 0.53 mm, p = 0.02), and smaller stent diameters (3.0 +/- 0.4 mm vs 3.4 +/- 0.5 mm, p <0.01). Plasma CRP levels at 48 hours (13.4 +/- 14.7 vs 5.9 +/- 4.9 mg/L, p <0.01) and 72 hours (16.7 +/- 19.8 vs 5.4 +/- 3.9 mg/L, p <0.01) after stent implantation were significantly higher in the BMS than in the DES group. In conclusion, DESs showed significantly lower plasma CRP levels after coronary stenting compared with BMSs. This may reflect the potent effects of DESs on acute inflammatory reactions induced by coronary intervention.

A randomized, open-label study to evaluate the efficacy and safety of pitavastatin compared with simvastatin in Korean patients with hypercholesterolemia.

BACKGROUND: Pitavastatin is a 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase inhibitor used to treat hypercholesterolemia. OBJECTIVE: The goal of this study was to compare the efficacy and safety of pitavastatin versus those of simvastatin in Korean patients with hypercholesterolemia. METHODS: This was an 8-week, multicenter, prospective, randomized, open-label, Phase III clinical trial. Male and female Korean patients with hypercholesterolemia who were between the ages of 20 and 75 years and who had a fasting triglyceride level <600 mg/dL and a low-density lipoprotein (LDL) cholesterol level >130 mg/dL after a 4-week dietary lead-in period were eligible for entry. Eligible patients were randomized into 2 groups in a 1:1 ratio. Patients received pitavastatin 2 mg once daily or simvastatin 20 mg once daily for 8 weeks. The medication was administered initially for 4 weeks, and an additional 4 weeks of study medication was prescribed at week 4. The final visit was conducted 8 weeks after randomization. RESULTS: Of the 104 patients randomized to treatment, 95 patients (59 women; 36 men) completed the study (49 in the pitavastatin group [mean age, 59.9 years] and 46 in the simvastatin group [mean age, 56.4 years]). No significant difference was found between groups with respect to patient age, sex, or body mass index. There was no significant difference in the percent decrease in LDL cholesterol levels (mean [SD], 38.2% [11.6%] decrease for the pitavastatin group vs 39.4% [12.9%] decrease for the simvastatin group [P = 0.648]). Also, there were no significant differences between the 2 study groups in the percent changes in total cholesterol, triglyceride, or high-density lipoprotein (HDL) cholesterol levels from baseline to study end. No significant difference was observed for the proportion of patients who achieved the LDL cholesterol goal of the National Cholesterol Education Program Adult Treatment Panel III: 93.9% (46/49) of patients in the pitavastatin group and 91.3% (42/46) of patients in the simvastatin group (P = 0.709) met the target level. At least 1 clinical adverse event and at least 1 adverse drug reaction were observed in 25.0% (13/52) and 11.5% (6/52), respectively, of patients in the pitavastatin group, and 37.3% (19/51) and 23.5% (12/51), respectively, in the simvastatin group; this difference was not statistically significant. The most common adverse event was an elevation in creatine kinase levels >2 times the upper limit of normal in 3.8% of pitavastatin-treated patients and 9.8% of simvastatin-treated patients (P = 0.269). There were no serious adverse drug reactions observed in either group. CONCLUSION: The HMG-CoA reductase inhibitor pitavastatin was found to be noninferior to simvastatin in terms of reducing LDL cholesterol, total cholesterol, and triglyceride levels, and increasing HDL cholesterol levels, in Korean patients with hypercholesterolemia after 8 weeks of treatment.

A beneficial effect of simvastatin on DNA damage in 242T allele of the NADPH oxidase p22phox in hypercholesterolemic patients.

BACKGROUND: The effect of simvastatin on DNA damage in hypercholesterolemic patients was investigated, and the relationship between the C242T polymorphism of the NADPH oxidase p22phox gene and the antioxidant effects of simvastatin was examined. METHODS: Simvastatin (20-40 mg /day) was administered for 8 weeks in 72 hypercholesterolemic patients. DNA damage in lymphocytes was quantified using single-cell gel electrophoresis (COMET assay) by measuring tail DNA (%), tail length (microm) and tail moment (tail length x % tail DNA/100). RESULTS: Simvastatin significantly reduced DNA damage as expressed by tail DNA (%, p< 0.001), tail length (mum, p<0.001) and tail moment on the DNA in lymphocytes (p<0.001) after 8 weeks. The frequencies of the C242T genotypes for CC, TC, and TT were 75.0%, 23.6% and 1.4% in the subjects. In the presence of the 242T allele, there were higher levels of baseline DNA damage and also a greater improvement in the DNA damage after 8 week simvastatin treatment compared with the CC homozygotes. CONCLUSION: Simvastatin significantly reduced DNA damage of hypercholesterolemic patients. This study showed that simvastatin has a beneficial effect on the improvement of DNA damage in patients with the 242T allele of NADPH oxidase p22phox gene.

The utility of multi-detector row spiral CT for detection of coronary artery stenoses.

Contrast-enhanced multi-detector row spiral computed tomography (MDCT) was introduced as a promising noninvasive method for vascular imaging. This study examined the accuracy of this technique for detecting significant coronary artery stenoses. Both MDCT(Sensation 16, Siemens, Germany, 12x0.75 mm collimation and 0.42 sec rotation speed, 120 kV, 500 effective mA, and 2.7 mm/rotation table-feed) and invasive coronary angiography (CAG) were performed on 61 patients (mean age 59.2+/-10, 44 men) who were suspected of having coronary artery disease. All patients were treated with atenolol (25-50 mg) prior to imaging and the heart rate was maintained below 65 beats per minutes during image acquisition. The images were reconstructed in the diastole around TI-400 ms with a 0.5 mm increment and a 1.0 mm thickness. All coronary arteries with a diameter of 2.0 mm or more were assessed for the presence of a stenosis (>50% luminal narrowing). Two independent radiologists who were unaware of the results of the invasive CAG evaluated the MDCT data, and the results were compared with those from the invasive CAG (interval 1-27, mean 11 days). An evaluation of the CT coronary angiogram (CTCA) was possible in 58 of the 61 patients (95%). Image acquisition of the major coronary arteries including the left main trunk was available in 229 out of 244 arteries. Invasive CAG showed that 35 out of 58 patients had significant coronary artery stenoses by. patient analysis of those who could be evaluated showed that CT coronary angiography correctly classified 30 out of 35 patients as having at least 1 coronary stenosis (sensitivity 85.7%, specificity 91.3%, positive predictive value 93.8%, negative predictive value 80.8%). By analyzing each coronary artery, CAG found 62 stenotic coronary arteries in the 229 coronary arteries that could be evaluated. MDCT correctly detected 50 out of 62 stenotic coronary arteries and an absence of stenosis was correctly identified in 156 out of 167 normal coronary arteries (sensitivity 80.6%, specificity 93.4%, positive predictive value 81.9%, negative predictive value 92.8%). The non-invasive technique of MDCT for examining the coronary artery appears to be a useful method for detecting coronary artery stenoses with a high accuracy particularly with the proximal portion and large arteries.